脑膜癌病的预后因素分析及T细胞亚群的免疫状态评估
发布时间：2019-05-19 07:48
【摘要】：目的:脑膜癌病(Meningeal carcinomatosis,MC)是恶性肿瘤细胞在脑脊液或脑膜多处种植的一种疾病。随着诊疗技术的提高,肿瘤患者的生存期延长,脑膜癌病的发病率越来越高。治疗脑膜癌病的主要目的是改善患者神经系统症状、延长患者生存期。本研究旨在总结脑膜癌病患者的临床特点,评估其预后因素及免疫功能状态。方法:回顾性分析2016年1月至2017年1月就诊于河北医科大学第二医院的35例脑膜癌病患者的临床资料。分析其临床特点;分析年龄、KPS(Karnofsky Performance Status)评分、原发癌症、脑脊液蛋白含量、是否合并脑积水、头颅增强核磁表现、是否进行鞘内联合靶向治疗、甲氨蝶呤剂量对患者预后的影响。测定患者外周血及脑脊液CD3+、CD3+CD4+、CD3+CD8+T细胞比例及CD3+CD4+/CD3+CD8+比值,并进行比较。结果:1脑膜癌病多见于中老年患者,多呈亚急性起病,河北省内地区分布以石家庄为主,原发癌以肺癌最常见,共20例,其次依次为胃癌7例,未明确肿瘤4例,乳腺癌、卵巢癌、前列腺癌、淋巴瘤各1例。临床表现多样,以高颅压症状最常见,共28例,颅神经受损的症状21例,表现为视力下降、视物成双、听力下降;脊髓或脊神经受损的症状12例,表现为颈背部疼痛、肢体无力、尿潴留;共济失调1例。35例行脑脊液细胞学检查,首次发现肿瘤细胞者30例(85.7%)。19例行头颅增强磁共振(Magnetic resonance imaging,MRI)检查,13例表现为软脑膜异常强化,其中6例同时存在脑实质强化结节。18例进行基因检测,6例表皮生长因子受体(epidermal growth factor receptor,EGFR)21突变;6例EGFR19突变;3例T790M突变。2 23例患者接受了标准的鞘内化疗方案,标准鞘内化疗甲氨蝶呤15mg组和10mg组,症状的缓解率分别87.50%、33.33%,差异有统计学意义(P=0.027)。3截止至2017年1月1日,随访35例患者,17例仍存活。中位生存时间7.54个月。Kaplan-Meier单因素分析显示原发癌种(P0.001)、是否合并脑积水(P=0.014)、KPS评分(P=0.001)及是否鞘内联合靶向治疗(P=0.001)与患者的预后相关。多因素分析显示KPS评分是影响脑膜癌病患者预后的独立因素。4对16例脑膜癌病患者外周血及脑脊液T细胞亚群进行分析,外周血CD8+T细胞比例大于正常值(P0.05),CD3+、CD4+T细胞及CD4+/CD8+比值与正常值比较无差异(P0.05)。而脑脊液CD3+、CD4+、CD8+T细胞比例高于正常值(P0.05),CD4+/CD8+比值低于正常值(P0.05),脑膜癌病患者外周血与脑脊液比较,脑脊液CD3+、CD4+、CD8+T细胞比例高于外周血(P0.05),CD4+/CD8+比值无差异(P0.05)。结论:1脑膜癌病多见于中老年人,常呈亚急性起病,河北省内患者主要集中于石家庄地区,原发癌以肺癌最常见。临床表现变化多端、无特异性。脑脊液细胞学是诊断此病的金标准,头颅MRI增强扫描有助于诊断,基因突变检测可指导用药。2鞘内化疗甲氨蝶呤15mg可改善患者的症状,临床医师可根据患者病情采用此剂量进行鞘内化疗。3原发癌种、是否合并脑积水、KPS评分及是否鞘内联合靶向治疗与患者的预后相关。KPS评分是影响脑膜癌病患者预后的独立因素。4 T细胞亚群检测可成为判读肿瘤患者细胞免疫状态的一种手段,检测脑膜癌患者脑脊液T细胞亚群数量可对其免疫状态评估有一定的临床意义。
[Abstract]:Objective: Meningeal carcinosis (MC) is a kind of disease in the cerebrospinal fluid or meninges of malignant tumor cells. With the improvement of the diagnosis and treatment technology, the survival time of the tumor patients is prolonged, and the incidence of meningeal cancer is higher and higher. The main purpose of the treatment of meningeal carcinomatosis is to improve the symptoms of the nervous system of the patient and prolong the survival time of the patients. The purpose of this study is to summarize the clinical features of meningocarcinoma and to assess the prognostic factors and immune function. Methods: The clinical data of 35 cases of meningocarcinoma in the second hospital from January 2016 to January 2017 were analyzed retrospectively. The clinical characteristics of the patients were analyzed. The age, the KPS (Karnofsky Performance Status) score, primary cancer, cerebrospinal fluid protein content, whether the hydrocephalus was combined, the magnetic performance of the head was enhanced, and the effect of the combination of the target therapy and the dose of methotrexate on the prognosis of the patients was investigated. The ratio of CD3 +, CD3 + CD4 +, CD3 + CD8 + T cells and the ratio of CD3 + CD4 +/ CD3 + CD8 + were determined and compared. Results:1. Meningeal carcinomatosis was found in middle-aged and old-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged patients. The distribution of primary cancer in Hebei province was mainly in Shijiazhuang. The primary cancer was the most common in lung cancer. 1 case of lymphoma. The clinical manifestations were diverse, with the most common symptoms of high-cranial pressure,28 cases, and 21 cases of cranial nerve damage, which showed that the visual acuity decreased, the visual acuity was double, the hearing decreased, and the symptoms of the spinal cord or the spinal cord were 12 cases, which showed the pain of the back of the neck, the weakness of the limbs and the retention of the urine; There were 30 cases of ataxia (85.7%) for the first time in 35 cases of ataxia.19 cases of brain-enhanced magnetic resonance (MRI) were examined, and 13 cases were abnormal enhancement of the meninges. In 6 of them, there were brain parenchyma strengthening nodules.18 cases were detected by gene,6 cases of epidermal growth factor receptor (EGFR)21 mutation,6 cases of EGFR19 mutation,3 cases of T790M mutation,23 of 23 patients received the standard intraoral chemotherapy, and 15 mg and 10 mg of the standard intraoral chemotherapy. The remission rate of the symptoms was 87.50%, 33.33%, and the difference was statistically significant (P = 0.027). The median survival time was 7.54 months. The Kaplan-Meier single-factor analysis showed that the primary cancer species (P0.001), the combined hydrocephalus (P = 0.014), the KPS score (P = 0.001), and the combined targeting treatment (P = 0.001) were associated with the patient's prognosis. Multi-factor analysis showed that the KPS score was an independent factor that affected the prognosis of the patients with meningeal cancer.4. The T-cell subsets in peripheral blood and cerebrospinal fluid of 16 patients with meningeal cancer were analyzed, and the ratio of CD8 + T cells in peripheral blood was higher than normal (P0.05), and CD3 +, There was no difference between the ratio of CD4 + T cells and CD4 +/ CD8 + to normal values (P0.05). The ratio of CD3 +, CD4 +, CD8 + T cells in the cerebrospinal fluid was higher than that of normal (P0.05). The ratio of CD4 +/ CD8 + was lower than normal (P0.05). The ratio of CD3 +, CD4 +, CD8 + T cells in the cerebrospinal fluid was higher than that of the peripheral blood (P0.05). The ratio of CD4 +/ CD8 + was not different (P0.05). Conclusion: Meningeal carcinomatosis is often seen in the middle-aged and the elderly, often subacute onset, and the patients in Hebei province are mainly concentrated in the Shijiazhuang area, and the primary cancer is the most common in the lung cancer. The clinical manifestations are variable and non-specific. Cerebrospinal fluid cytology is a gold standard for the diagnosis of the disease. The MRI-enhanced scan of the skull is helpful to the diagnosis and gene mutation detection. The 15 mg of methotrexate can improve the symptoms of the patient. The clinical physician can use this dose for intraoral chemotherapy according to the condition of the patient. Whether the combined hydrocephalus, the KPS score, and the combined targeting therapy in the patients were associated with the patient's prognosis. KPS score is an independent factor that affects the prognosis of patients with meningeal cancer.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R739.45
本文编号：2480531
[Abstract]:Objective: Meningeal carcinosis (MC) is a kind of disease in the cerebrospinal fluid or meninges of malignant tumor cells. With the improvement of the diagnosis and treatment technology, the survival time of the tumor patients is prolonged, and the incidence of meningeal cancer is higher and higher. The main purpose of the treatment of meningeal carcinomatosis is to improve the symptoms of the nervous system of the patient and prolong the survival time of the patients. The purpose of this study is to summarize the clinical features of meningocarcinoma and to assess the prognostic factors and immune function. Methods: The clinical data of 35 cases of meningocarcinoma in the second hospital from January 2016 to January 2017 were analyzed retrospectively. The clinical characteristics of the patients were analyzed. The age, the KPS (Karnofsky Performance Status) score, primary cancer, cerebrospinal fluid protein content, whether the hydrocephalus was combined, the magnetic performance of the head was enhanced, and the effect of the combination of the target therapy and the dose of methotrexate on the prognosis of the patients was investigated. The ratio of CD3 +, CD3 + CD4 +, CD3 + CD8 + T cells and the ratio of CD3 + CD4 +/ CD3 + CD8 + were determined and compared. Results:1. Meningeal carcinomatosis was found in middle-aged and old-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged and middle-aged patients. The distribution of primary cancer in Hebei province was mainly in Shijiazhuang. The primary cancer was the most common in lung cancer. 1 case of lymphoma. The clinical manifestations were diverse, with the most common symptoms of high-cranial pressure,28 cases, and 21 cases of cranial nerve damage, which showed that the visual acuity decreased, the visual acuity was double, the hearing decreased, and the symptoms of the spinal cord or the spinal cord were 12 cases, which showed the pain of the back of the neck, the weakness of the limbs and the retention of the urine; There were 30 cases of ataxia (85.7%) for the first time in 35 cases of ataxia.19 cases of brain-enhanced magnetic resonance (MRI) were examined, and 13 cases were abnormal enhancement of the meninges. In 6 of them, there were brain parenchyma strengthening nodules.18 cases were detected by gene,6 cases of epidermal growth factor receptor (EGFR)21 mutation,6 cases of EGFR19 mutation,3 cases of T790M mutation,23 of 23 patients received the standard intraoral chemotherapy, and 15 mg and 10 mg of the standard intraoral chemotherapy. The remission rate of the symptoms was 87.50%, 33.33%, and the difference was statistically significant (P = 0.027). The median survival time was 7.54 months. The Kaplan-Meier single-factor analysis showed that the primary cancer species (P0.001), the combined hydrocephalus (P = 0.014), the KPS score (P = 0.001), and the combined targeting treatment (P = 0.001) were associated with the patient's prognosis. Multi-factor analysis showed that the KPS score was an independent factor that affected the prognosis of the patients with meningeal cancer.4. The T-cell subsets in peripheral blood and cerebrospinal fluid of 16 patients with meningeal cancer were analyzed, and the ratio of CD8 + T cells in peripheral blood was higher than normal (P0.05), and CD3 +, There was no difference between the ratio of CD4 + T cells and CD4 +/ CD8 + to normal values (P0.05). The ratio of CD3 +, CD4 +, CD8 + T cells in the cerebrospinal fluid was higher than that of normal (P0.05). The ratio of CD4 +/ CD8 + was lower than normal (P0.05). The ratio of CD3 +, CD4 +, CD8 + T cells in the cerebrospinal fluid was higher than that of the peripheral blood (P0.05). The ratio of CD4 +/ CD8 + was not different (P0.05). Conclusion: Meningeal carcinomatosis is often seen in the middle-aged and the elderly, often subacute onset, and the patients in Hebei province are mainly concentrated in the Shijiazhuang area, and the primary cancer is the most common in the lung cancer. The clinical manifestations are variable and non-specific. Cerebrospinal fluid cytology is a gold standard for the diagnosis of the disease. The MRI-enhanced scan of the skull is helpful to the diagnosis and gene mutation detection. The 15 mg of methotrexate can improve the symptoms of the patient. The clinical physician can use this dose for intraoral chemotherapy according to the condition of the patient. Whether the combined hydrocephalus, the KPS score, and the combined targeting therapy in the patients were associated with the patient's prognosis. KPS score is an independent factor that affects the prognosis of patients with meningeal cancer.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R739.45
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